Neurological Erdheim-Chester Disease Manifesting with Subacute or Progressive Cerebellar Ataxia: Novel Case Series and Review of the Literature

Abstract

Neurological involvement is relatively common in Erdheim-Chester disease (ECD), a rare clonal disorder of histiocytic myeloid precursors characterized by multisystem involvement. In ECD patients, neurological symptoms can occur either at onset or during the disease course and may lead to various degrees of neurological disability or affect patients' life expectancy. The clinical neurological presentation of ECD often consists of cerebellar symptoms, showing either a subacute or progressive course. In this latter case, patients manifest with a slowly progressive cerebellar ataxia, variably associated with other non-specific neurological signs, infratentorial leukoencephalopathy, and cerebellar atrophy, possibly mimicking either adult-onset degenerative or immune-mediated ataxia. In such cases, diagnosis of ECD may be particularly challenging, yet some peculiar features are helpful to address it. Here, we retrospectively describe four novel ECD patients, all manifesting cerebellar symptoms at onset. In two cases, slow disease progression and associated brain MRI features simulated a degenerative cerebellar ataxia. Three patients received a definite diagnosis of histiocytosis, whereas one case lacked histology confirmation, although clinical diagnostic features were strongly suggestive. Our findings regarding existing literature data focused on neurological ECD will be also discussed to highlight those diagnostic clues helpful to address diagnosis.

Keywords: Erdheim–Chester disease; cerebellar ataxia; histiocytosis; neurohistiocytosis.

Figure 1

Panel showing brain MRI of Pt #1 (A–C), Pt #3 (D–F), and Pt #4 (G–I). (A) Transverse FLAIR scan (pons level) of Pt #1 showing mild hyperintensity of the pons, both MCPs, dentate nuclei. (B) Transverse SWAN scan (mesencephalon level) of Pt #1 showing marked hypointense signal (metal deposits) of bilateral substantia nigra. (C) Sagittal T2-weighted scan of Pt #1 showing slight vermian cerebellar atrophy. (D) Transverse FLAIR scan (pons level) of Pt #3 showing hyperintensity of the pons and dentate nuclei. (E) Transverse SWAN scan (thalami level) of Pt #3 showing marked hypointense signal (metal deposits) of putamina and globi pallidi. (F) Sagittal T2-weighted scan of Pt #3 showing vermian cerebellar atrophy. (G) Transverse FLAIR scan (pons level) of Pt #4 showing hyperintensity of the pons and both MCPs. (H) Transverse FLAIR scan (mesencephalon level) of Pt #4 showing hyperintensity of the mesencephalon and parahippocampal cortices. (I) Coronal T2-weighted scan of Pt #4 showing hyperintensity of the pons, both SCPs and MCPs. Abbreviations: Flair: fluid-attenuated inversion recovery; MCP: middle cerebellar peduncle; SWAN: susceptibility-weighted angiography; SCP: superior cerebellar peduncle.

Figure 2

Panel showing brain MRI of Patient #2. (A) Sagittal T2-weighted scan showing one nodular lesion along with extensive hyperintensity of the white matter of the RCH, the ipsilateral MCP, and the pons. (B) Transverse T2-weighted scan (pons level) showing the same nodular hypointense lesion with hyperintensity of the white matter of the RCH, both MCPs and the pons. (C) Transverse T1-weighted scan (pons level) showing marked, homogeneous contrast enhancement of the RCH nodular lesion. Abbreviations: RCH: right cerebellar hemisphere; MCP: middle cerebellar peduncle.